Aminomethyl piperidine

Methoxy-5-nitrophenyl)perhydropyrido[ 1,2-a]pyrazin-3-one was obtained by cyclization of l-(ethoxycarbonylmethyl)-2-[A-(2-methoxy-5-nitrophenyl)aminomethyl]piperidine on the action of NaH in boiling dioxane (99MIP10). 

A solution of 192 g of 1 -phenethyl-4-hydroxy-4-aminomethyl piperidine in BOO cc of diethyi-carbonate is heated for 1 /i hours to refiux at about B0°C in the presence of sodium methylate (prepared for immediate use from 2 g of sodium). After this time, the ethyl alcohol formed during the reaction is slowly distilled while the maximum temperature is reached. The excess ethyl carbonate is distilled under reduced pressure. A crystallized residue Is then obtained, which is stirred with 400 cc of water and 400 cc of ether. The solution is filtered and 125 g (77.6%) of practically pure product melting at 232°C to 233°C, are obtained. 

Fig. 13 (a) Possible structures of hyperbranched polymer (p(X-Y)) from the conjugate addition of X (diacrylate) and Y (trifunctional amines), (b) Structures of diacrylates and trifunctional amine monomers used for the synthesis 4-(aminomethyl)piperidine) (AMP), A-methylethylenediamine (MEDA), l-(2-aminoethyl)piperazine (AEPZ), ethylene glycol diacrylate (EGDA), 1,4-butanediol diacrylate (BDDA), and 1,6-hexanediol diacrylate (HDDA). Adapted with permission from [124], Copyright 2005 Elsevier... 

Reactions of 3-substituted 2-(lV-phenylaminomethyl)piperazines with a slight excess of ethyl 2-chloroacetate under reflux afforded mixtures of 9-substituted 2-phenylperhydropyrido[l,2-a]pyrazin-3- and -4-ones, which could be separated by column chromatography [72JCS(P2)1374], When 2-[(3-trifluoromethylphenyl)aminomethyl]piperidine was heated with optically active ethyl 2-chloropropionate (87MIP1 91TA231), or lactic acid ethyl ester methanesulphonate (91TA231), the product was a C-9a epimeric mixture of 2-(3-trifluoromethylphenyl)-4-methylperhydropyrido[l,2-fl]-pyrazin-3-ones. The reaction between yV-methyl-2-piperidine-carboxamide and hydroxymaleic anhydride in pyridine resulted in 2,3-dimethyl-3-hydroxyperhydropyrido[l,2-a]pyrazine-l,4-dione (74CB2804). 

A recently reported synthesis sequence [152] starts from MeOPEG-bound 4-fluoro-3-nitro-benzoic acid. After the nucleophilic aromatic substitution of the fluorine with piperazine, homopiperazine and 4-aminomethyl-piperidine (only the secondary amino group reacted) the remaining free amino function was acylated or sulfonated. 

Kurihara and coworkers at Toray Industries prepared several aminated derivatives of polyepichlorohydrin, then formed composite polyamide membranes by interfacial reaction with isophthaloyl chloride.38 Polyepichlorohydrin was converted to polyepiiodohydrin, then reacted with either4-(aminomethyl)piperidine, 3-(methylamino)hexahydroazepine, or 3-(amino)hexahydroazepine. Also, poly-epiaminohydrin was prepared by reduction of the azide derivative of polyepiiodohydrin. Best salt rejections were obtained if the polymeric amine formulation contained a substantial proportion of the monomeric amines as coreactants in the interfacial reaction. In tests on 3.5% sodium chloride at 800 psi and 25 C, salt rejections of 99.5% at fluxes of 8 to 9 gfd were characteristic. A three-zone barrier layer was produced, consisting of a heat-crosslinked polyamine gel (as in NS-100), a polyamide layer incorporating both the polymeric... 

Methyl-oyolohexylhydrazin 16, 66,1 22. f-[y-Amino.propyl]-pyrro)idin 20 II6. N.[. Amlno- thyI]-pipeTidjn 20, 67, II42. X-Amlno-eay-lupetidin 20, 108, X-Amlno-a.a. lupetidin 20, 109. I Me l-S-aminomethyl-piperidin... 

Compound 72 was then successfully captured by theFmoc-cystein-loaded Wang resin at the ClAc tag in the presence of diisopropylethylamine (DIPEA). After washing the resin, 73 was released from the resin by Fmoc deprotection with 4-(aminomethyl)piperidine followed by the spontaneous intramolecular cyclization to afford 74 with excellent purity... 

Nucleophilic substitution reactions of PEG-bound benzylic chloride were easily monitored by NMR spectroscopy. For example, Fig. 3 shows a typical change in chemical shift during the nucleophilic substitution reaction with piperidine. After the coupling reaction was completed, the benzylic protons (8 4.61 ppm, marked as ) of immobilized benzyl chloride 2 completely disappeared and were shifted upfield into the PEG protons absorption area ( 8 3.4-3.8 ppm), but no change was observed in the aromatic region. This evidence showed complete transformation of 2 to a PEG bound amine. Similar results were also obtained by employing other nucleophiles such as piperazine, 4-(aminomethyl)piperidine, and homopiperazine. 

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